1.1- Disubstituted dienes

A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

The FMO approach shown in Figure 15.19 again indicates that the 4s - - 2s interaction should lead directly to formation of two new bonding a-bonds, i.e. this is an allowed reaction. The preference for a concerted 4s + 2s reaction is experimentally supported by observations which show that the stereochemistry of the diene and dieneophile is carried over to the product, e.g. a trans,frans-l,4-disubstituted diene... 

Early work on the microstructurc of the diene polymers has been reviewed.1 While polymerizations of a large number of 2-substituted and 2,3-disubstituted dienes have been reported,88 little is known about the microstructure of diene polymers other than PB,89 polyisoprene,90 and polychloroprene.91... 

With respect to 1,4-disubstituted dienes, fewer cases have been investigated, but here too the reaction is stereospecific and syn. Thus, transjrans-lA-diphenylbutadiene gives cis- 1,4-diphenylcyclohexene derivatives. 

So in the transition state, the terminal carbon atoms of the diene must move in the disrotatory manner so that the HOMO of S02 can interact with the LUMO of diene or the LUMO of S02 with the HOMO of diene. This is why trans, trans 1, 4 disubstituted dienes give 3 substituted sulphones. 

Ab initio calculations of 2,3-disubstituted dienes have predicted that the tram conformation is more stable than the cis conformation. Results of these calculations are shown in Table 21. 

Cycloadditions of nitroso compounds and 1,3-dienes lead to 3,6-dihydro-2//- 1,2-oxazines this is a well tried and documented procedure (B-67MI22700), a comparatively modern example of which is the regiospecific synthesis of 2,3,4-trisubstituted derivatives (155) from the addition of nitrosobenzenes to 1,2-disubstituted dienes (154) (78T697). 

With 1,4-disubstituted dienes, more complex stereochemistry is possible in the polymers. In addition to the possibility of geometrical isomerism, there are two types of completely assymetric centre in the molecule and tritactic polymers can... 

Pd(PPh3)4-catalysed isomerization of methylenecyclopropanes in acetic acid proceeds smoothly at 1-substituted or 1,1-disubstituted dienes (Scheme 90). A plausible mechanism is hydropalladation and /3-carbon-Pd elimination followed by /3-hydride elimination, established from a deuterium labelling experiment.133... 

Both compounds bear a 1,3-disubstituted diene, proving that RCM occurs through the intermolecular ene-yne metathesis pathway (Scheme 2.21), which is usually the case for rings of size 12 or greater. 

Radical addition/cross-coupling products 61 were obtained in 60-91% yield when Ni(dppf)Cl2 was applied as a catalyst in reactions of alkyl halides 60 with 2,3-disubstituted dienes 59 and aryl Grignard or arylzinc reagents (Fig. 12). Competition experiments of n-, sec-, and ferf-butyl bromide with 2,3-dimethylbutadiene... 

Terminal alkynes and terminal alkenes can be selectively transformed into disubstituted dienes in the presence of ruthenium carbene complexes [94-96]. Reactions of a series of alkynes with H2C=CHCH2SiMe3 lead to silyl-substi-tuted conjugated dienes. 

To our knowledge, the first example reported of a tellurium-lithium exchange reaction leading to a vinyllithium was the reaction of 2,5-diphenyltellurophene 165 with -butyllithium, giving l,4-dilithium-l,4-diphenylbuta-l,3-diene 166, which was trapped with several electrophiles leading to the corresponding disubstituted dienes 167 with retention of configuration (Scheme 95).254... 

Nitroso compounds generally react as dienophiles with 1,3-dienes to give 3.6-dihydro-2//-1,2-ox-azines 1 through a [4 -I- 2] addition proceeding in a stereoselective cis mode. The overall process, carried out on cyclic or 1,4-disubstituted dienes, consists of a diastereoselective 1,4-oxyamination of the diene moiety1 - 3. 

Total simple diastereoselectivity is observed in the hetero-Diels-Alder cycloaddition of nitro-soarencs to 1,3-dienes leading to the corresponding 3,6-dihydro-2//-l, 2-oxazines. A number of acyclic 1,4-disubstituted dienes have been reacted with nitrosoarenes, but the stereochemistry of the adduct 1 has not been assigned 6 s. 

Finally, ( )-2-chloro-8a-cyano-dccahydro-2-nitrosonaphthalcnc (7), readily obtained by treating rra .s-8a-cyano-octahydro-2(l//)-naphthalenone with tert-butyl hypochlorite, undergoes hetcro-cycloaddition with 1,4-disubstituted dienes leading stereoselectively to a single product 8 in good yield40. 

For non-symmetrical monosubstituted dienes and dienophiles the preferential formation of isomers, 329 or 330 correspondingly, is usually observed. The transition state for 1,4-disubstituted dienes may be formed via endo or exo orientation of the reactants and thus two isomeric products could be produced. Typically, the endo transition state is favored and the respective endo adducts produced, as is shown for the preparation of the nearly individual endo isomer 331a. 

The Lewis acid-promoted reaction of our oximinosulfonate with dienes and the conversion of the resulting cycloadducts to pyridines comprises a new annulation method for the synthesis of substituted pyridines from conjugated dienes. As illustrated in the Table, very good overall yields are obtained in reactions of 2-substituted dienes, providing 5-substituted pyridine-2-carboxylates. Reactions with 1-substituted dienes yield 3-substituted pyridines, and disubstituted dienes react smoothly to afford trisubstituted pyridines in good yield. Polycyclic systems are obtained when dienes such as 1-vinyl-1-cyclohexene are employed in the annulation. 

Rearrangement processes of alkyltitanocene dichlorides that occur under electron impact have been investigated using deuterium labelling. A novel type of zirconium-mediated coupling reaction of alkynes with vinyl bromide to afford 2,3-disubstituted dienes has been reported (see Scheme 105), and an inter-intramolecular reaction sequence has been proposed for the observed formation of vinylcyclohexadienes and/or methylenecycloheptadienes from the copper-catalysed reaction of zirconacyclo-pentadienes with allylic dichlorides. The essential step in these processes appears to be transmetallation of the zirconium-carbon bond of the zirconacyclopentadiene to produce a more reactive copper-carbon bond. New phosphorus heterocycles, e.g. (417), have been constructed by the thermal rearrangement of a [l,4-bis(trimethylsilyl)->/ -cyclooctatetraene]- ,3,5-triphospha-7-hafhanorbomadiene complex (416). 

Cyclization of 1,5-diketones linked by a methylthiomethyl chain gives dihydrothiophenes (74), which upon oxidation and elimination provide stereodefined 1,3-dienes (equation 103). Thus, meso diketones give cis,cis 1,4-disubstituted dienes whilst ( )-diketones give the trans,cis isomers. 

The preceding discussion is not meant to imply that stereo electronic effects alone are responsible for determining diastereoselection in the Diels-Alder reaction. Indeed, examples of reactions that do not conform to the endo rule abound, and these cases are not easily explained without invoking alternative hypotheses. For instance, it has been demonstrated that 1,1-disubstituted dien-ophiles can favor formation of the exo product with cyclopentadiene, sometimes to the complete exclusion of the electronically favored endo isomer [19]. There appears to be subtle interplay between steric and electronic factors, as simply switching the diene to cyclohexadiene or an acyclic diene results in a turnover in selectivity to favor the endo isomer. While the exact source of stereocontrol for a given cycloaddition is still a source of debate, this review will emphasize the practical ramifications of diastereoselection, namely, prototypical dienophiles such as a-methacrolein and a-bromoacrolein can be relied on to deliver exo cycloadducts preferentially with cyclopentadiene endo otherwise), while acrylate, crotonate, and cinnamate-derived dienophiles will generally favor the endo tran-... 

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